Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

Ivan P Mosiagin; Olesya A Tomashenko; Dar'ya V Spiridonova; Mikhail S Novikov; Sergey P Tunik; Alexander F Khlebnikov

doi:10.3762/bjoc.17.105

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

Beilstein J Org Chem. 2021 Jun 23:17:1490-1498. doi: 10.3762/bjoc.17.105. eCollection 2021.

Authors

Ivan P Mosiagin¹, Olesya A Tomashenko¹, Dar'ya V Spiridonova¹, Mikhail S Novikov¹, Sergey P Tunik¹, Alexander F Khlebnikov¹

Affiliation

¹ Saint Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab., St. Petersburg 199034, Russia.

Abstract

A wide range of derivatives with new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o-bromophenyl-substituted pyrrolylpyridinium salts using the (TMS)₃SiH/AIBN system. The cyclization provides generally good yields of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline hydrobromides having no additional radical-sensitive substituents. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at room temperature. The selectivity control of intramolecular arylation was achieved by replacing the halogen: the use of 1-(2-(ortho-bromophenyl)-4-(ortho-iodophenyl)pyrrol-3-yl)pyridinium bromide makes it possible to obtain a monocyclization product, and the bicyclization product from the dibromo derivative. The procedure is also applicable to obtain 3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinoline derivatives including 2-unsubstituted skeletons that are inaccessible via Pd-catalyzed cyclization.

Keywords: arylation; pyridine; pyrrole; radical cyclization; tris(trimethylsilyl)silane.

Grants and funding

We gratefully acknowledge the financial support of the Russian Science Foundation project 16-13-10036. This research was carried out using resources of the Centre for Magnetic Resonance, the Research Centre for X-ray Diffraction Studies, the Centre for Chemical Analysis and Materials, and the Computer Centre of the Science Park of Saint Petersburg State University.